Optical techniques for tissue diagnosis without removal of tissue are now being developed which offer significant advantages over standard techniques, such as tissue biopsy, both in terms of patient care and medical costs. For example, optical techniques are faster, sedatives are not needed, and complications associated with tissue removal such as infection are eliminated. A wide range of techniques has been investigated for tissue diagnosis including Raman, fluorescence, and elastic-scatter spectroscopy. The potential of elastic-scatter and fluorescence spectroscopy has been demonstrated in clinical trials in vivo. Sensitivities and specificities in the upper 90th percentile have been reported for some forms of cancer in the bladder and esophagus based on empirically determined metrics. This work will focus on continuous-wave elastic-scatter spectroscopy in the near-ultraviolet (NUV), visible, and near-infrared (NIR). This technique has the advantage of being simple and inexpensive to implement and is sensitive to both morphological and structural features of tissue. The ability of elastic-light transport measurements, made in endoscopically compatible geometries, to detect average microscopic features of cells will be investigated. A detailed study will be performed of light scattering properties of in vitro tissue models which retain biochemical and morphological characteristics of cells in tissues, but lack the additional complicating factors of tissue structure, and vascular architecture. Initial experiments will concentrate on scattering and absorption properties of malignant and nonmalignant cell suspensions. Subsequently, elastic-scatter measurements will be performed using more realistic tissue models that have controllable heterogeneity such as multicellular spheroids. The experimental work will be integrated with Monte Carlo simulations of light transport. These simulations will be used to predict how specific characteristics of the media being measured, such as the probability distribution of scattering angles, density of scatterers, and heterogeneities determine the elastic-scatter signal.